The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice
- PMID: 18973473
- PMCID: PMC2752860
- DOI: 10.1042/BJ20081304
The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice
Abstract
STAF [Sec (selenocysteine) tRNA gene transcription activating factor] is a transcription activating factor for a number of RNA Pol III- and RNA Pol II-dependent genes including the Trsp [Sec tRNA gene], which in turn controls the expression of all selenoproteins. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined. We generated transgenic mice expressing the Trsp transgene lacking the STAF-binding site and made these mice dependent on the transgene for survival by removing the wild-type Trsp. The level of Sec tRNA was unaffected or slightly elevated in heart and testis, but reduced approximately 60% in liver and kidney, approximately 70% in lung and spleen and approximately 80% in brain and muscle compared with the corresponding organs in control mice. Moreover, the ratio of the two isoforms of Sec tRNA that differ by methylation at position 34 (Um34) was altered significantly, and the Um34-containing form was substantially reduced in all tissues examined. Selenoprotein expression in these animals was most affected in tissues in which the Sec tRNA levels were most severely reduced. Importantly, mice had a neurological phenotype strikingly similar to that of mice in which the selenoprotein P gene had been removed and their life span was substantially reduced. The results indicate that STAF influences selenoprotein expression by enhancing Trsp synthesis in an organ-specific manner and by controlling Sec tRNA modification in each tissue examined.
Figures
Similar articles
-
Selective restoration of the selenoprotein population in a mouse hepatocyte selenoproteinless background with different mutant selenocysteine tRNAs lacking Um34.J Biol Chem. 2007 Nov 9;282(45):32591-602. doi: 10.1074/jbc.M707036200. Epub 2007 Sep 11. J Biol Chem. 2007. PMID: 17848557
-
Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA.Mol Cell Biol. 2001 Jun;21(11):3840-52. doi: 10.1128/MCB.21.11.3840-3852.2001. Mol Cell Biol. 2001. PMID: 11340175 Free PMC article.
-
Deletion of the selenocysteine tRNA gene in macrophages and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2.J Biol Chem. 2008 Jan 25;283(4):2021-30. doi: 10.1074/jbc.M708352200. Epub 2007 Nov 26. J Biol Chem. 2008. PMID: 18039655
-
Selenocysteine tRNAs as central components of selenoprotein biosynthesis in eukaryotes.Biomed Environ Sci. 1997 Sep;10(2-3):116-24. Biomed Environ Sci. 1997. PMID: 9315302 Review.
-
Update on selenoprotein biosynthesis.Antioxid Redox Signal. 2015 Oct 1;23(10):775-94. doi: 10.1089/ars.2015.6391. Epub 2015 Aug 25. Antioxid Redox Signal. 2015. PMID: 26154496 Review.
Cited by
-
Historical Roles of Selenium and Selenoproteins in Health and Development: The Good, the Bad and the Ugly.Int J Mol Sci. 2021 Dec 21;23(1):5. doi: 10.3390/ijms23010005. Int J Mol Sci. 2021. PMID: 35008430 Free PMC article. Review.
-
The Effect of tRNA[Ser]Sec Isopentenylation on Selenoprotein Expression.Int J Mol Sci. 2021 Oct 23;22(21):11454. doi: 10.3390/ijms222111454. Int J Mol Sci. 2021. PMID: 34768885 Free PMC article.
-
The Neurobiology of Selenium: Looking Back and to the Future.Front Neurosci. 2021 Feb 25;15:652099. doi: 10.3389/fnins.2021.652099. eCollection 2021. Front Neurosci. 2021. PMID: 33732108 Free PMC article. Review.
-
march5 Governs the Convergence and Extension Movement for Organization of the Telencephalon and Diencephalon in Zebrafish Embryos.Mol Cells. 2020 Jan 31;43(1):76-85. doi: 10.14348/molcells.2019.0210. Mol Cells. 2020. PMID: 31910335 Free PMC article.
-
Selenocysteine β-Lyase: Biochemistry, Regulation and Physiological Role of the Selenocysteine Decomposition Enzyme.Antioxidants (Basel). 2019 Sep 1;8(9):357. doi: 10.3390/antiox8090357. Antioxidants (Basel). 2019. PMID: 31480609 Free PMC article. Review.
References
-
- Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN. Characterization of mammalian selenoproteomes. Science. 2003;300:1439–1443. - PubMed
-
- Hatfield DL, Choi IS, Ohama T, Jung J-E, Diamond AM. Selenocysteine tRNA[Ser]Sec isoacceptors as central components in selenoprotein biosynthesis in eukaryotes. In: Burk RF, editor. Selenium in Biology and Human Health. Springer-Verlag; New York: 1994. pp. 25–44.
-
- Hatfield DL, Carlson BA, Xu XM, Mix H, Gladyshev VN. Selenocysteine incorporation machinery and the role of selenoproteins in development and health. Prog. Nucleic Acid Res. Mol. Biol. 2006;81:97–142. - PubMed
-
- Moustafa ME, Carlson BA, El-Saadani MA, Kryukov GV, Sun QA, Harney JW, Hill KE, Combs GF, Feigenbaum L, Mansur DB, et al. Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA. Mol. Cell. Biol. 2001;21:3840–3852. - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases